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1.
YL Wu DT Chu B Han X Liu L Zhang C Zhou M Liao T Mok H Jiang E Duffield M Fukuoka 《Asia-Pacific Journal of Clinical Oncology》2012,8(3):232-243
Aim: In the IRESSA Pan‐Asia Study (IPASS), 1217 patients in East Asia with pulmonary adenocarcinoma who were never‐smokers or ex/light‐smokers received first‐line gefitinib (250 mg/day) or carboplatin/paclitaxel (area under the curve 5/6; 200 mg/m2). Efficacy analyses were pre‐planned in patients in China. Methods: In China, 372 patients (30.6% of the overall group) were randomized. The primary end‐point was progression‐free survival (PFS). Secondary end‐points were overall survival (OS), objective response rate (ORR), health‐related quality of life (HRQoL), symptom improvement, safety and tolerability. Results: For patients in China, PFS did not significantly differ from the overall IPASS population (interaction test P= 0.427). PFS was numerically longer (hazard ratio [HR] 0.79; 95% CI 0.62–1.01; P= 0.065; median PFS 6.8 months for both treatments) and ORR significantly higher (ORR 44.6 vs 29.8%; odds ratio 1.88; 95% CI 1.22–2.89; P= 0.004) for gefitinib than carboplatin/paclitaxel. OS (mature data) was similar for both treatments (HR 0.92; 95% CI 0.73–1.17; P= 0.511; median OS gefitinib 18.1 months vs 18.3 months carboplatin/paclitaxel). HRQoL improvement rates favored gefitinib; symptom improvement rates were similar for both treatments. Gefitinib had a more favorable tolerability profile than carboplatin/paclitaxel. Efficacy by epidermal growth factor receptor biomarker status (exploratory analyses) was difficult to interpret due to low patient numbers with known biomarker status. Conclusion: For the Chinese subgroup of IPASS, gefitinib demonstrated improved PFS and ORR, similar OS, higher HRQoL, similar symptom improvement rates and a more favorable tolerability profile than carboplatin/paclitaxel, generally consistent with the overall IPASS population. 相似文献
2.
Yung‐Jue Bang Chung‐Pin Li Kyung‐Hun Lee Chang‐Fang Chiu Joon Oh Park Yan‐Shen Shan Jun Suk Kim Jen‐Shi Chen Hyun‐Jeong Shim Kun‐Ming Rau Hye Jin Choi Do‐Youn Oh Bruce Belanger Li‐Tzong Chen 《Cancer science》2020,111(2):513-527
The global, randomized NAPOLI‐1 phase 3 trial reported a survival benefit with liposomal irinotecan (nal‐IRI) plus 5‐fluorouracil/leucovorin (nal‐IRI+5‐FU/LV) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) after previous gemcitabine‐based therapy. Median overall survival (OS) with nal‐IRI+5‐FU/LV was 6.1 vs 4.2 months with 5‐FU/LV alone (unstratified hazard ratio [HR] = 0.67, P = .012). Herein, we report efficacy and safety results from a post‐hoc subgroup analysis of Asian patients treated at Asian centers. Primary study endpoint was OS; secondary endpoints included progression‐free survival (PFS), objective response rate (ORR), and safety. Patients receiving nal‐IRI+5‐FU/LV (n = 34) had significantly longer median OS versus 5‐FU/LV (n = 35) (8.9 vs 3.7 months; unstratified HR = 0.51, P = .025). Patients had significantly increased median PFS with nal‐IRI+5‐FU/LV versus 5‐FU/LV (4.0 vs 1.4; unstratified HR = 0.48, P = .011), and increased ORR (8.8% vs 0; P = .114). nal‐IRI monotherapy (n = 50) numerically improved efficacy endpoints versus 5‐FU/LV (n = 48): median OS was 5.8 versus 4.3 months (HR = 0.83, P = .423) and median PFS was 2.8 versus 1.4 months (HR = 0.69, P = .155). Grade ≥3 neutropenia was reported more frequently with nal‐IRI+5‐FU/LV versus 5‐FU/LV (54.5% vs 3.4%), and incidence of grade ≥3 diarrhea was comparable between the two arms (3.0% vs 6.9%). This subgroup analysis confirms nal‐IRI+5‐FU/LV as an efficacious treatment option that improves survival in Asian patients with mPDAC that progressed after gemcitabine‐based therapy, with a safety profile agreeing with previous findings. The nal‐IRI+5‐FU/LV regimen should represent a new standard of care for these patients in Asia. (Clinicaltrials.gov: NCT01494506) 相似文献
3.
Shujuan Zhou Yongyong Ma Yifen Shi Liyuan Tang Zhouyi Zheng Fang Fang Jianhua Feng Yu Zhang Lan Sun Yi Chen Bin Liang Songfu Jiang Zhijian Shen Kang Yu Siqian Wang 《Hematological oncology》2018,36(1):104-109
To determine the prognostic value of baseline mean platelet volume (MPV) in diffuse large B‐cell lymphoma (DLBCL) patients. We retrospectively analyzed 161 DLBCL patients who received R‐CHOP chemotherapy. The associations between MPV and clinicopathological factors were assessed. A low MPV (MPV ≤ 9.1 fl, cut‐off was calculated by receiver operating characteristics) was not associated with any other clinicopathological factors. * Patients with MPV ≤ 9.1 fl experienced a shorter progression‐free survival (PFS) (2‐year PFS rate, 60.6% vs 84.0%, P = 0.003) and overall survival (OS) (2‐year OS rate, 70.4% vs 87.9%, P = 0.030), compared with those with MPV > 9.1 fl. The multivariate analysis demonstrated that MPV ≤ 9.1 fl was an independent prognostic factor of OS (Hazard Ratio [HR] = 0.588, P = 0.045) and PFS (HR = 0.456, P = 0.010). Therefore, we demonstrated that low baseline MPV is an independent prognostic marker of poor outcome in patients with DLBCL. 相似文献
4.
Randomized phase II study of nab‐paclitaxel as first‐line chemotherapy in patients with HER2‐negative metastatic breast cancer
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Kenji Tamura Kenichi Inoue Norikazu Masuda Shintaro Takao Masahiro Kashiwaba Yutaka Tokuda Hiroji Iwata Naohito Yamamoto Kenjiro Aogi Toshiaki Saeki Takahiro Nakayama Nobuaki Sato Tatsuya Toyama Takanori Ishida Hitoshi Arioka Mitsue Saito Shinji Ohno Hideko Yamauchi Kimito Yamada Junichiro Watanabe Hiroshi Ishiguro Yasuhiro Fujiwara 《Cancer science》2017,108(5):987-994
Weekly administration of nanoparticle albumin‐bound paclitaxel (nab‐paclitaxel) has been shown to be a safe and effective treatment for metastatic breast cancer (MBC) in clinical studies. We conducted a multicenter, randomized, open‐label phase II study to compare the efficacy and safety of weekly nab‐paclitaxel and docetaxel in Japanese patients with human epidermal growth factor receptor 2‐negative MBC. The primary endpoint was progression‐free survival (PFS). Patients were randomized to receive nab‐paclitaxel (150 mg/m2 nab‐paclitaxel once per week for 3 of 4 weeks; n = 100) or docetaxel (75 mg/m2 docetaxel every 3 weeks; n = 100). The median PFS by independent radiologist assessment was 9.8 months (90% confidence interval [CI]: 8.5–11.2) for nab‐paclitaxel and 11.2 months (90% CI: 8.4–13.8) for docetaxel (hazard ratio: 1.25, P = 0.363), and the median overall survival was 42.4 months and 34.0 months, respectively. The overall response rate was 56.1% for nab‐paclitaxel and 52.5% for docetaxel. Adverse events in both treatment arms were similar to previous reports. Neutropenia was the most common adverse event in both arms, with 35.0% of patients in the nab‐paclitaxel arm and 89.0% in the docetaxel arm experiencing grade 4 neutropenia. Grade 3 peripheral sensory neuropathy occurred in 22.0% of patients in the nab‐paclitaxel and 5.0% in the docetaxel arm. In this study, although weekly nab‐paclitaxel 150 mg/m2 did not show superiority in PFS compared with docetaxel, efficacy outcomes were similar in patients treated with weekly nab‐paclitaxel and docetaxel. 相似文献
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6.
Mao‐Bin Meng Huan‐Huan Wang Nicholas G. Zaorsky Bing‐Shen Sun Lei Zhu Yong‐Chun Song Feng‐Tong Li Yang Dong Jing‐Sheng Wang Hua‐Ming Chen Xu‐Yao Yu Zhi‐Yong Yuan 《Cancer science》2019,110(11):3553-3564
To determine the therapeutic efficacy and safety of risk‐adapted stereotactic body radiation therapy (SBRT) schedules for patients with early‐stage central and ultra‐central inoperable non‐small cell lung cancer. From 2006 to 2015, 80 inoperable T1‐2N0M0 NSCLC patients were treated with two median dose levels: 60 Gy in six fractions (range, 48‐60 Gy in 4‐8 fractions) prescribed to the 74% isodose line (range, 58%‐79%) for central lesions (ie within 2 cm of, but not abutting, the proximal bronchial tree; n = 43), and 56 Gy in seven fractions (range, 48‐60 Gy in 5‐10 fractions) prescribed to the 74% isodose line (range, 60%‐80%) for ultra‐central lesions (ie abutting the proximal bronchial tree; n = 37) on consecutive days. Primary endpoint was overall survival (OS); secondary endpoints included progression‐free survival (PFS), tumor local control rate (LC), and toxicity. Median OS and PFS were 64.47 and 32.10 months (respectively) for ultra‐central patients, and not reached for central patients. Median time to local failure, regional failure, and any distant failures for central versus ultra‐central lesions were: 27.37 versus 26.07 months, 20.90 versus 12.53 months, and 20.85 versus 15.53 months, respectively, all P < .05. Multivariate analyses showed that tumor categorization (ultra‐central) and planning target volume ≥52.76 mL were poor prognostic factors of OS, PFS, and LC, respectively (all P < .05). There was one grade 5 toxicity; all other toxicities were grade 1‐2. Our results showed that ultra‐central tumors have a poor OS, PFS, and LC compared with central patients because of the use of risk‐adapted SBRT schedules that allow for equal and favorable toxicity profiles. 相似文献
7.
Prognostic value of 18F‐fluoroazomycin arabinoside PET/CT in patients with advanced non‐small‐cell lung cancer
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Tsuneo Saga Masayuki Inubushi Mitsuru Koizumi Kyosan Yoshikawa Ming‐Rong Zhang Katsuyuki Tanimoto Atsushi Horiike Noriko Yanagitani Fumiyoshi Ohyanagi Makoto Nishio 《Cancer science》2015,106(11):1554-1560
This study evaluated the prognostic value of positron emission tomography/computed tomography (PET/CT) using 18F‐fluoroazomycin arabinoside (FAZA) in patients with advanced non‐small‐cell lung cancer (NSCLC) compared with 18F‐fluorodeoxyglucose (FDG). Thirty‐eight patients with advanced NSCLC (stage III, 23 patients; stage IV, 15 patients) underwent FAZA and FDG PET/CT before treatment. The PET parameters (tumor‐to‐muscle ratio [T/M] at 1 and 2 h for FAZA, maximum standardized uptake value for FDG) in the primary lesion and lymph node (LN) metastasis and clinical parameters were compared concerning their effects on progression‐free survival (PFS) and overall survival (OS). In our univariate analysis of all patients, clinical stage and FAZA T/M in LNs at 1 and 2 h were predictive of PFS (P = 0.021, 0.028, and 0.002, respectively). Multivariate analysis also indicated that clinical stage and FAZA T/M in LNs at 1 and 2 h were independent predictors of PFS. Subgroup analysis of chemoradiotherapy‐treated stage III patients revealed that only FAZA T/M in LNs at 2 h was predictive of PFS (P = 0.025). The FDG PET/CT parameters were not predictive of PFS. No parameter was a significant predictor of OS. In patients with advanced NSCLC, FAZA uptake in LNs, but not in primary lesions, was predictive of treatment outcome. These results suggest the importance of characterization of LN metastases in advanced NSCLC patients. 相似文献
8.
Chunxiang Cao Xunlei Zhang Meng Kuang Dongying Gu Mingliang He Jinfei Chen Cuiju Tang 《Cancer science》2014,105(8):1008-1014
Whether S‐1 could replace 5‐Fluorouracil (5‐Fu) or not in the treatment of advanced gastrointestinal (GI) cancer (including advanced gastric cancer [AGS] and metastatic colorectal cancer [mCRC]) in Asian patients has been controversial. This meta‐analysis was performed to compare the activity, efficacy and toxicity of S‐1‐based versus 5‐Fu‐based chemotherapy in those Asian patients. Randomized controlled trials (RCTs) were identified by electronic search of Pubmed. Relevant abstracts were manually searched to identify relevant trials. A total of 2182 patients from eight RCTs were included, and our results demonstrated that S‐1‐based chemotherapy significantly improved overall survival (OS) (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.77–1.00) and overall response rate (ORR) (odds ratio [OR], 1.72; 95% CI, 1.09–2.70), but no significant progression‐free survival (PFS) benefit was found between arms (HR, 0.87; 95% CI, 0.72–1.06). Subgroup analyses revealed that S‐1‐based chemotherapy significantly improved OS and ORR in subgroups of patients with non‐platinum containing regimens (P = 0.041; P = 0.034) and patients with no prior chemotherapy history (P = 0.025; P = 0.016). Statistically significant improvements of PFS and ORR in the S‐1‐based chemotherapy were observed in the subgroup of patients with AGC (P < 0.001; P = 0.005). S‐1‐based chemotherapy was characterized by significantly higher incidences of diarrhea, fatigue and thrombocytopenia, and a lower incidence of nausea. This analysis provided strong evidence for survival benefits of S‐1, and S‐1‐based chemotherapy could be considered to replace 5‐Fu‐based therapy for the treatment of advanced GI cancer in Asian patients. 相似文献
9.
10.
Akiko Miyagi Maeshima Hirokazu Taniguchi Suguru Fukuhara Noriyuki Morikawa Wataru Munakata Dai Maruyama Sung‐Won Kim Takashi Watanabe Yukio Kobayashi Kensei Tobinai Hitoshi Tsuda 《Cancer science》2012,103(10):1898-1904
This study aimed to clarify the clinicopathological prognostic parameters of de novo diffuse large B‐cell lymphoma (DLBCL) in the rituximab era. We examined the correlation of 22 clinicopathological parameters with progression‐free survival (PFS), overall survival (OS), and primary refractory disease in 285 DLBCL patients treated with rituximab‐containing chemotherapy. Complete response rate was 87%, overall response rate was 91%, 5‐year PFS rate was 72%, and 5‐year OS rate was 91%. By log–rank test, higher International Prognostic Index (IPI) (P < 0.0001), Bcl‐2 positivity (P = 0.0013), Bcl‐6 negativity (P = 0.0112), and no irradiation (P = 0.0371) were significantly correlated with shorter PFS; higher IPI (P = 0.0107), starry sky pattern (P = 0.0466), and no irradiation (P = 0.0264) correlated with shorter OS. In multivariate analyses, higher IPI (P = 0.0006), Bcl‐2 positivity (P = 0.0015), and Bcl‐6 negativity (P = 0.04) were significantly correlated with shorter PFS; higher IPI (P = 0.0045) correlated with shorter OS. Bcl‐2 (P = 0.0029), Bcl‐6 (P = 0.002), and IPI (P < 0.0001) were significantly correlated with primary refractory disease. In conclusion, Bcl‐2 positivity, Bcl‐6 negativity, and higher IPI were indicators of shorter PFS and OS plus primary refractory disease in patients with DLBCL in the rituximab era. 相似文献
11.
Mayu Shiomi Shinya Matsuzaki Satoshi Serada Koji Matsuo Chihiro Mizuta-Odani Mariko Jitsumori Ruriko Nakae Satoko Matsuzaki Satoshi Nakagawa Kosuke Hiramatsu Ai Miyoshi Eiji Kobayashi Toshihiro Kimura Yutaka Ueda Kiyoshi Yoshino Tetsuji Naka Tadashi Kimura 《Cancer science》2021,112(9):3655-3668
This study aimed to investigate the cytotoxicity of a cluster of differentiation 70 antibody-drug conjugate (CD70-ADC) against ovarian cancer in in vitro and in vivo xenograft models. CD70 expression was assessed in clinical samples by immunohistochemical analysis. Western blotting and fluorescence-activated cell sorting analyses were used to determine CD70 expression in the ovarian cancer cell lines A2780 and SKOV3, and in the cisplatin-resistant ovarian cancer cell lines A2780cisR and SKOV3cisR. CD70 expression after cisplatin exposure was determined in A2780 cells transfected with mock- or nuclear factor (NF)-κB-p65-small interfering RNA. We developed an ADC with an anti-CD70 monoclonal antibody linked to monomethyl auristatin F and investigated its cytotoxic effect. We examined 63 ovarian cancer clinical samples; 43 (68.3%) of them expressed CD70. Among patients with advanced stage disease (n = 50), those who received neoadjuvant chemotherapy were more likely to exhibit high CD70 expression compared to those who did not (55.6% [15/27] vs 17.4% [4/23], P < .01). CD70 expression was confirmed in A2780cisR, SKOV3, and SKOV3cisR cells. Notably, CD70 expression was induced after cisplatin treatment in A2780 mock cells but not in A2780-NF-κB-p65-silenced cells. CD70-ADC was cytotoxic to A2780cisR, SKOV3, and SKOV3cisR cells, with IC50 values ranging from 0.104 to 0.341 nmol/L. In A2780cisR and SKOV3cisR xenograft models, tumor growth in CD70-ADC treated mice was significantly inhibited compared to that in the control-ADC treated mice (A2780cisR: 32.0 vs 1639.0 mm3, P < .01; SKOV3cisR: 232.2 vs 584.9 mm3, P < .01). Platinum treatment induced CD70 expression in ovarian cancer cells. CD70-ADC may have potential therapeutic implications in the treatment of CD70 expressing ovarian cancer. 相似文献
12.
Hiroshi Yagi Fusanori Yotsumoto Kenzo Sonoda Masahide Kuroki Eisuke Mekada Shingo Miyamoto 《International journal of cancer. Journal international du cancer》2009,124(6):1429-1439
Heparin‐binding EGF‐like growth factor (HB‐EGF) plays a pivotal role in tumor growth and clinical outcomes in patients with ovarian cancer, leading to the validation of HB‐EGF as a target for ovarian cancer therapy. In this study, we investigated the anti‐tumor effects of paclitaxel, as an anti‐cancer agent, and CRM197, as a specific inhibitor off HB‐EGF, in ovarian cancer. Paclitaxel induced transient ERK activation and sustained activation of JNK and p38 MAPK through the ectodomain shedding of HB‐EGF in SKOV3 cells. In addition, the overexpression of HB‐EGF in paclitaxel‐treated SKOV3 cells resulted in modulation of paclitaxel‐evoked MAPK signaling, including marked activation of ERK and Akt, and minimized activation of JNK and p38 MAPK, indicating that HB‐EGF is involved in drug sensitivity through the balance of anti‐apoptotic and pro‐apoptotic signals induced by paclitaxel. The combination of paclitaxel with CRM197 had an inhibitory effect on cell proliferation and enhanced apoptosis via the inhibition of ERK and Akt activation and the stimulation of p38 and JNK activation. More prominently, the administration of paclitaxel with CRM197 resulted in synergistic anti‐tumor effects in SKOV3 cells and in SKOV3 cells overexpressing HB‐EGF in xenografted mice. Accordingly, inhibitory agents against HB‐EGF, such as CRM197, represent possible chemotherapeutic and chemosensitizing agents for ovarian cancer. © 2008 Wiley‐Liss, Inc. 相似文献
13.
Chanjuan Xie Xinming Yin Yueqin Liu Yuan Cao Yue Fang Xin Lin Yao Xu Wenlin Xu Huiling Shen Jian Wen 《International journal of cancer. Journal international du cancer》2014,135(6):1286-1296
Multidrug resistance (MDR) remains a major obstacle to effective chemotherapy treatment in ovarian cancer. In our study, paclitaxel‐resistant ovarian cancer patients and cell lines had decreased miR‐145 levels and expressed high levels of Sp1 and Cdk6. Introducing miR‐145 into SKOV3/PTX and A2780/PTX cells led to a reduction in Cdk6 and Sp1 along with downregulation of P‐gp and pRb. These changes resulted in increased accumulation of antineoplastic drugs and G1 cell cycle arrest, which rendered the cells more sensitive to paclitaxel in vitro and in vivo. These effects could be reversed by reintroducing Sp1 or Cdk6 into cells expressing high levels of miR‐145, resulting in restoration of P‐gp and pRb levels. Furthermore, we confirmed that both Cdk6 and Sp1 are targets of miR‐145. Intriguingly, demethylation with 5‐aza‐dC led to reactivation of miR‐145 expression in drug‐resistant ovarian cancer cell lines, which also resulted in increased sensitivity to paclitaxel. Collectively, these findings begin to elucidate the role of miR‐145 as an important regulator of chemoresistance in ovarian cancer by controlling both Cdk6 and Sp1. 相似文献
14.
Ruby Yun-Ju Huang Kuan-Ju Huang Ko-Chen Chen Sheng-Mou Hsiao Tuan Zea Tan Chin-Jui Wu Ching Hsu Wen-Chun Chang Chen-Yu Pan Bor-Ching Sheu Lin-Hung Wei 《International journal of cancer. Journal international du cancer》2023,152(10):2174-2185
Ovarian clear cell carcinoma (OCCC) is a distinct histotype of ovarian cancer, which usually presages a worse prognosis upon recurrence. Identifying patients at risk for relapse is an unmet need to improve outcomes. A retrospective cohort analysis of 195 early-stage OCCC patients diagnosed between January 2011 and December 2019 at National Taiwan University Hospital was conducted to identify prognostic factors for recurrence, progression-free survival (PFS) and overall survival (OS). Molecular profiling of tumors was performed in a case-controlled cohort matched for adjuvant therapy for biomarker discovery. Multivariate Cox proportional hazard model revealed that paclitaxel-based chemotherapy was associated with better PFS than nonpaclitaxel chemotherapy (HR = 0.19, P = .006). The addition of bevacizumab was associated with better PFS, compared to no bevacizumab (HR = 0.09, P = .02). Neither showed significant improvement in OS. Recurrence is associated with an Immune-Hot tumor feature (P = .03), the CTLA-4-high subtype (P = .01) and increased infiltration of immune cells in general. The Immune-Hot feature (HR = 3.39, P = .005) and the CTLA-4-high subtype (HR = 2.13, P = .059) were associated with worse PFS. Immune-Hot tumor features could prognosticate recurrence in early-stage OCCC. 相似文献
15.
Kavita K. Mishra Sarah Squire Kathleen Lamborn Anuradha Banerjee Nalin Gupta William M. Wara Michael D. Prados Mitchel S. Berger Daphne A. Haas-Kogan 《Journal of neuro-oncology》2010,100(1):121-127
To report long-term results for children with low-grade hypothalamic/chiasmatic gliomas treated on a phase II chemotherapy
protocol. Between 1984 and 1992, 33 children with hypothalamic/chiasmatic LGGs received TPDCV chemotherapy on a phase II prospective
trial. Median age was 3.0 years (range 0.3–16.2). Twelve patients (36%) underwent STRs, 14 (42%) biopsy only, and seven (21%)
no surgery. Twenty patients (61%) had pathologic JPAs, nine (27%) grade II gliomas, and four (12%) no surgical sampling. Median
f/u for surviving patients was 15.2 years (range 5.3–20.7); 20 of the 23 surviving patients had 14 or more years of follow-up.
Fifteen-year PFS and OS were 23.4 and 71.2%, respectively. Twenty-five patients progressed, of whom 13 are NED, two are AWD,
and 10 have died. All children who died were diagnosed and first treated at age three or younger. Age at diagnosis was significantly
associated with relapse and survival (P = 0.004 for PFS and P = 0.037 for OS). No PFS or OS benefit was seen with STR versus biopsy/no sampling (P = 0.58 for PFS, P = 0.59 for OS). For patients with JPAs and WHO grade II tumors, the 15-year PFS was 18.8 and 22.2% (P = 0.95) and 15-year OS was 73.7 and 55.6% (P = 0.17), respectively. Upfront TPDCV for children with hypothalamic/chiasmatic LGGs resulted in 15-year OS of 71.2% and 15-year
PFS of 23.4%. No survival benefit is demonstrated for greater extent of resection. Age is a significant prognostic factor
for progression and survival. 相似文献
16.
Afatinib versus cisplatin plus pemetrexed in Japanese patients with advanced non‐small cell lung cancer harboring activating EGFR mutations: Subgroup analysis of LUX‐Lung 3
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Terufumi Kato Hiroshige Yoshioka Isamu Okamoto Akira Yokoyama Toyoaki Hida Takashi Seto Katsuyuki Kiura Dan Massey Yoko Seki Nobuyuki Yamamoto 《Cancer science》2015,106(9):1202-1211
In LUX‐Lung 3, afatinib significantly improved progression‐free survival (PFS) versus cisplatin/pemetrexed in EGFR mutation‐positive lung adenocarcinoma patients and overall survival (OS) in Del19 patients. Preplanned analyses in Japanese patients from LUX‐Lung 3 were performed. Patients were randomized 2:1 to afatinib or cisplatin/pemetrexed, stratified by mutation type (Del19/L858R/Other). Primary endpoint was PFS (independent review). Secondary endpoints included OS, objective response, and safety. Median PFS (data cut‐off: February 2012) for afatinib versus cisplatin/pemetrexed was 13.8 vs 6.9 months (hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.20–0.70; P = 0.0014) in all Japanese patients (N = 83), with more pronounced improvements in those with common mutations (Del19/L858R; HR, 0.28; 95% CI, 0.15–0.52; P < 0.0001) and Del19 mutations (HR, 0.16; 95% CI, 0.06–0.39; P < 0.0001). PFS was also improved in L858R patients (HR, 0.50; 95% CI, 0.20–1.25; P = 0.1309). Median OS (data cut‐off: November 2013) with afatinib versus cisplatin/pemetrexed was 46.9 vs 35.8 months (HR, 0.75; 95% CI, 0.40–1.43; P = 0.3791) in all Japanese patients, with greater benefit in patients with common mutations (HR, 0.57; 95% CI, 0.29–1.12; P = 0.0966) and Del19 mutations (HR, 0.34; 95% CI, 0.13–0.87; P = 0.0181); OS was not significantly different in L858R patients (HR, 1.13; 95% CI, 0.40–3.21; P = 0.8212). Following study treatment discontinuation, most patients (93.5%) received subsequent anticancer therapy. The most common treatment‐related adverse events were diarrhea, rash/acne, nail effects and stomatitis with afatinib and nausea, decreased appetite, neutropenia, and leukopenia with cisplatin/pemetrexed. Afatinib significantly improved PFS versus cisplatin/pemetrexed in Japanese EGFR mutation‐positive lung adenocarcinoma patients and OS in Del19 but not L858R patients ( www.clinicaltrials.gov ; NCT00949650). 相似文献
17.
Prolonged survival after second autologous transplantation and lenalidomide maintenance for salvage treatment of myeloma patients at first relapse after prior autograft
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Ursina Gössi Barbara Jeker Behrouz Mansouri Taleghani Ulrike Bacher Urban Novak Daniel Betticher Thomas Egger Thilo Zander Thomas Pabst 《Hematological oncology》2018,36(2):436-444
Autologous stem cell transplantation (ASCT) as part of the primary therapy in multiple myeloma (MM) is standard practice. In contrast, the role of a second ASCT (ASCT2) and subsequent lenalidomide maintenance for relapsed disease remains unclear. In this study, we analysed 86 consecutive MM patients with a first relapse after prior ASCT receiving either a second ASCT or conventional chemotherapy. After a median follow‐up of 37.7 months since first relapse, 54 (62.8%) patients were still alive and 29 (33.7%) without progression. Sixty‐one (71.0%) patients received ASCT2 and had better progression‐free survival (PFS) (30.2 versus 13.0 mo; P = .0262) and overall survival (OS) rates (129.6 versus 33.5 mo; P = .0003) compared with 25 (29.0%) patients with conventional treatment. Patients relapsing later than 12 months after ASCT1 benefitted from a second ASCT with better PFS2 (P = .0179) and OS2 (P = .0009). Finally, lenalidomide maintenance after ASCT2 was associated with longer PFS (41.0 vs 21.6 mo; P = .0034) and better OS (not yet reached vs 129.6 mo; P = .0434) compared with patients without maintenance. Our data suggest that a second ASCT and lenalidomide maintenance given at first relapse in MM after prior ASCT are associated with better survival rates. 相似文献
18.
Cao Yang Francis J. Hornicek Kirkham B. Wood Joseph H. Schwab Henry Mankin Zhenfeng Duan 《Cancer chemotherapy and pharmacology》2009,64(3):607-614
Purpose To identify the apoptosis genes involved in the multidrug resistant phenotype of osteosarcoma.
Methods Multidrug resistant human osteosarcoma cell line (U-2 OS MR) and a drug sensitive parental cell line (U-2 OS) were both treated
with paclitaxel and analyzed by the gene array containing 96 apoptosis associated genes. The different expression of the special
apoptosis associated genes were further analyzed by Western blot in the multidrug resistant osteosarcoma cell lines (U-2 OS
MR, KH OS R2) and the drug sensitive parental cell lines (U-2 OS, KH OS). One of the disregulated gene, RAIDD, was transfected
into the multidrug resistant osteosarcoma cells for functional studies.
Results RAIDD showed signs of significant expression in the U-2 OS cells after being treated with paclitaxel (P < 0.01). However, the induction of RAIDD did not occur in U-2 OS MR cells (P = 0.2). Subsequent analysis by Western blot confirmed the deficiency of the expression of RAIDD protein in U-2 OS MR. On
the contrary, the expression of RAIDD could be significantly induced by paclitaxel and doxorubicin in U-2 OS cells as both
time and dosage were deciding factors. It also demonstrated the cleavage of PARP associated with RAIDD expression in U-2 OS
cells, but not however in U-2 OS MR cells after being treated with paclitaxel or doxorubicin. Similar results were found in
osteosarcoma multidrug resistant cell line KH OS R2 and the drug sensitive parental cell line KH OS. Furthermore, over-expression
of RAIDD in multidrug resistant cell lines could possibly reverse drug resistant phenotypes.
Conclusion This study indicate that impaired expression of RAIDD in drug induced apoptosis may play a role in the multidrug resistance
of osteosarcoma cells. 相似文献
19.
Akiko M. Maeshima Hirokazu Taniguchi Suguru Fukuhara Dai Maruyama Sung‐Won Kim Takashi Watanabe Yukio Kobayashi Kensei Tobinai Hitoshi Tsuda 《Cancer science》2013,104(7):952-957
Follicular lymphoma (FL) frequently transforms into diffuse large B‐cell lymphoma (DLBCL). To clarify the associated clinicopathological prognostic parameters, we examined the correlation of 11 histopathological parameters with progression‐free survival (PFS) and overall survival (OS) in 107 consecutive patients who had DLBCL with pre‐existing (asynchronous) or synchronous FL. The patients comprised 58 men and 49 women with a median age of 56 years. For DLBCL, the complete response rate was 81%, overall response rate was 88%, and 5‐year PFS and OS rates were 55% and 79%, respectively. Immunohistochemical analysis of the DLBCL component revealed the following positivity rates: CD10, 64%; Bcl‐2, 83%; Bcl‐6, 88%; MUM1, 42%; GCB, 82%; cMyc index ≥80%, 17%; and Ki‐67 index ≥90%, 19%. IGH/BCL2 fusion was positive in 57% of DLBCL cases. In univariate analyses, asynchronous FL and DLBCL (24%, P = 0.021), 100% proportion of DLBCL (29%, P = 0.004), Bcl‐2 positivity (P = 0.04), and high Ki‐67 index (P = 0.003) were significantly correlated with shorter PFS. Asynchronous FL and DLBCL (P = 0.003), 100% proportion of DLBCL (P = 0.001), and high Ki‐67 index (P = 0.004) were significantly correlated with shorter OS. In a multivariate analysis, asynchronous FL and DLBCL (P = 0.035) and 100% proportion of DLBCL (P = 0.016) were significantly correlated with shorter OS. Thus, asynchronism and 100% proportion of DLBCL, that is, FL relapsed as pure DLBCL, or FL and DLBCL at different sites, were significant predictors of unfavorable outcome of patients with DLBCL transformed from FL. 相似文献
20.
Audrey Mailliez Veronique D'Hondt Amelie Lusque Olivier Caron Luc Cabel Anthony Goncalves Marc Debled Laurence Gladieff Jean-Marc Ferrero Thierry Petit Marie Ange Mouret-Reynier Jean-Christophe Eymard Christelle Levy Lionel Uwer Marianne Leheurteur Isabelle Desmoulins Thomas Bachelot Jean-Sebastien Frenel Thibault de la Motte Rouge Gaëtane Simon William Jacot Suzette Delaloge 《International journal of cancer. Journal international du cancer》2023,152(5):921-931
The outcomes and best treatment strategies for germline BRCA1/2 mutation (gBRCAm) carriers with metastatic breast cancer (MBC) remain uncertain. We compared the overall survival and the first line progression free survival (PFS1) of patients with a gBRCAm identified at initiation of first-line treatment with those of BRCA wild-type (WT) and not-tested (NT) individuals in the ESME real-world database of MBC patients between 2008 and 2016 (NCT03275311). Among the 20 624 eligible patients, 325 had a gBRCAm, 1138 were WT and 19 161 NT. Compared with WT, gBRCAm carriers were younger, and had more aggressive diseases. At a median follow-up of 50.5 months, median OS was 30.6 (95%CI: 21.9-34.3), 35.8 (95%CI: 32.2-37.8) and 39.3 months (95% CI: 38.3-40.3) in the gBRCAm, WT and NT subgroups, respectively. Median PFS1 was 7.9 (95%CI: 6.6-9.3), 7.8 (95%CI: 7.3-8.5) and 9.7 months (95%CI, 9.5-10.0). In the multivariable analysis conducted in the whole cohort, gBRCAm status had however no independent prognostic impact on OS and PFS1. Though, in the triple-negative subgroup, gBRCAm patients had better OS and PFS1 (HR vs WT = 0.76; 95%CI: 0.60-0.97; P = .027 and 0.69; 95% CI: 0.55-0.86; P = .001, respectively). In contrast, in patients with HR+/HER2 negative cancers, PFS1 appeared significantly and OS non significantly lower for gBRCAm carriers (PFS1: HR vs WT = 1.23; 95%CI: 1.03-1.46; P = .024; OS:HR = 1.22, 95% CI: 0.97-1.52, P = .089). In conclusion, gBRCA1/2 status appears to have divergent survival effects in MBC according to IHC subtype. 相似文献